Surface-modified sensor device and method for surface-modifying the same

ABSTRACT

A method for surface-modifying a sensor device is disclosed, which includes the following steps: providing a sensor device, wherein a surface of the sensor device has a metal film; forming a surface-modification layer having a plurality of carboxyl groups on the metal film of the sensor device by isopropyl alcohol plasma; and forming a poly(acrylic acid) layer on the surface-modification layer, wherein the acrylic acid of the poly(acrylic acid) layer is grafted to the carboxyl of the surface-modification layer. A surface-modified sensor device is also disclosed.

This patent application is a continuation-in-part (CIP) of U.S. patentapplication Ser. No. 12/153,911, filed May 28, 2008, entitled “Methodfor Biomolecule Immobilization”, herein incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a surface-modified sensor device and amethod for surface-modifying a sensor device and, more particularly, toa surface-modified sensor device with increased density of bondedmolecules and uniformity and a method for surface-modifying a sensordevice.

2. Description of Related Art

In recent years, the application of optical sensors has become a majortrend in biomolecule detection for medical diagnosis and film thicknessmeasurement. In the biomolecule detection, the biomolecules are requiredto be immobilized on the sensor devices and then reacted with the testsample to provide a signal variation for the determination of thespecies and amount of the test sample.

If the biomolecules require to be immobilized on the metal coatings ofthe optical sensors, the metal coatings need to be modified first. Inthe conventional surface modification for the biomolecules, the opticalsensors are immersed in an 11-mercaptoundecanoic acid (MUA) solution. Byway of the immersion, it is expected that the lone pair of sulfur in MUAwill occupy an outer vacant orbital of a metal atom to form a stablecoordination bond therebetween. Accordingly, carboxyl groups (COOH) areformed on the metal coatings to achieve the modification thereof.Subsequently, the carboxyl groups of the surface modification layer arebonded to biomolecules in the presence of a coupling activator,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) N-hydroxysuccinimide(NHS), to realize biomolecule immobilization.

Nevertheless, such chemical modification of immersion in MUA involvesconsiderable reaction time and causes the metal coatings to have unevensurface hydrophilicity, leading to undesirable result of themodification. Accordingly, the modification cannot achieve theanticipated level and has drawbacks such as long waiting time, increasedexperimental instability, and reduced uniformity.

Therefore, it is desirable to provide a method for surface-modifying asensor device to give the metal coating of the sensor device uniformsurface hydrophilicity so that the detection properties, sensitivity,and so on of the sensor device can be improved to benefit the accuracyof the of the biomolecule detection.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method forsurface-modifying a sensor device. The method can increase the number ofcarboxyl groups and hydrophilicity of the surface of the sensor device,thereby enhancing the immobilization of the biomolecules.

To achieve the object, one aspect of the present invention provides amethod for surface-modifying a sensor device including the followingsteps: providing a sensor device, wherein a surface of the sensor devicehas a metal film; forming a surface-modification layer having aplurality of carboxyl groups on the metal film of the sensor device byisopropyl alcohol plasma; and forming a poly(acrylic acid) layer on thesurface-modification layer, wherein the acrylic acid of the poly(acrylicacid) layer is grafted to the carboxyl groups of thesurface-modification layer.

In the abovementioned method of the present invention, after thetreatment of isopropyl alcohol plasma, carboxyl groups (COOH) can beformed on the metal film of the sensor device and subsequently graftedwith acrylic acid by polymerization so that a poly(acrylic acid) layercan be formed on the sensor device. Meanwhile, the time for performanceof the plasma modification can be in a range from 1 to 30 minutes, orfrom 5 to 15 minutes. During the performance of the plasma modification,the strength of watts or pressure can be determined on the kind of theplasma, the time of the performance, and so on.

Compared with a sensor device modified only with isopropyl alcoholplasma, much more carboxylic groups, more uniform distribution of thecarboxylic groups, and better hydrophilicity are introduced in thesensor device of the present invention treated with the combination ofthe isopropyl alcohol plasma modification and the acrylic acidpolymerization so as to benefit subsequent immobilization ofbio-molecules, leading to improvement of sensitivity and detectionproperties of the sensor device.

In the abovementioned method for surface-modifying a sensor device, thekind of the sensor device is not limited and it can be, for example, anoptical fiber sensor device. Also, the kind of the metal film on thesensor device is not limited. However, the metal film can be a gold orsilver film in order to give the optical sensor device a preferablereaction. In general, a gold film is used as the metal film. Thethickness of the film is not limited and is preferably in a range from20 nm to 80 nm, for example 40±5 nm. The formation of the film is alsonot limited and it can be any manner used by a person skilled in the artof the present invention, for example electroplating or arranging metalnanoballs to form a film.

Therefore, if a metal film on a sensing area of an optical fiber sensordevice is treated with the method of the present invention and thenbio-molecules are immobilized thereon, this device can be used to detecta sample according to surface plasmon resonance (SPR).

The abovementioned method for surface-modifying a sensor device canfurther include the following step: forming a bio-molecule layer on thepoly(acrylic acid) layer, wherein bio-molecules of the bio-moleculelayer are bonded to the carboxyl groups of poly(acrylic acid) of thepoly(acrylic acid) layer.

The aforesaid bio-molecules can be antibodies, antigens, enzymes, partsof tissues, or single cells. For example, since protein A or serumalbumin is able to bind to the Fc region of an antibody, an antigen canbe specifically recognized by the antibody bonded to the protein A orserum albumin (serving as the bio-molecules) immobilized on the thinmetal film. Hence, the optical sensors modified in the abovementionedmethod can specifically detect the antigen recognized by the antibodybonded to the protein A or serum albumin, and thus identify the antigenand its concentration.

In the abovementioned method for surface-modifying a sensor device ofthe present invention, the biomolecules of the bio-molecule layer arebonded to the poly(acrylic acid) layer in the presence of a couplingactivator. The coupling activator can be selected from a groupconsisting of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC),N-hydroxy-succinimide (NHS), and a combination thereof.

In the abovementioned method for surface-modifying a sensor device, saidpoly(acrylic acid) grafted with the carboxyl groups can be formed by thepolymerization of acrylic acid under UV illumination. In other words,under UV illumination, grafting polymerization of acrylic acid iscarried on to make poly(acrylic acid) be grafted the carboxyl groups ofthe surface modification layer. Accordingly, more and uniform carboxylgroups can be formed on the sensor device.

Another object of the present invention is to provide a surface-modifiedsensor device to give better detection properties, sensitivity etc. soas to promote the accuracy of the biomolecule detection.

In order to achieve the object mentioned above, another aspect of thepresent invention provides a surface-modified sensor device including: asensor device, on which a metal film is disposed; a surface-modificationlayer having a plurality of carboxyl groups on the metal film of thesensor device, wherein the surface-modification layer is formed byisopropyl alcohol plasma; and a poly(acrylic acid) layer on thesurface-modification layer, wherein the acrylic acid of the poly(acrylicacid) layer is grafted to the carboxyl groups of thesurface-modification layer.

The surface-modified sensor device of the present invention said abovecan further include: a bio-molecule layer located on the poly(acrylicacid) layer, wherein bio-molecules of the bio-molecule layer are bondedto the carboxyl groups of poly(acrylic acid) of the poly(acrylic acid)layer. Particularly, the biomolecules are not limited and they can beprotein A or serum albumin. Besides, the biomolecules of thebio-molecule layer can be bonded to the poly(acrylic acid) layer in thepresence of a coupling activator.

In the surface-modified sensor device of the present invention, themetal film can be a gold or silver film, and the poly(acrylic acid)layer can be formed by the polymerization of acrylic acid under UVillumination.

In conclusion, the present invention combines surface modification ofisopropyl alcohol plasma and grafting polymerization of acrylic acid topromote the stability of the manufacturing and efficiently control thedensity of the bonding molecules. In addition, the surface modificationformed by isopropyl alcohol plasma has considerable and evenlydistributing carboxyl groups and low porosity, and thus exhibits goodcoverage and adherence to the metal film of the sensor device.Furthermore, grafting polymerization of acrylic acid is carried on toform a poly(acrylic acid) layer on the surface modification layer tointroduce more carboxyl groups uniformly distributing on the sensordevice. Therefore, the surface hydrophilicity of the sensor device issignificantly enhanced. Also, the increase in the number of the carboxylgroups can benefit the subsequent immobilization of the biomolecules soas to improve the detection properties and accuracy of the sensordevice.

Other objects, advantages, and novel features of the invention willbecome more apparent from the following detailed description when takenin conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A to 1D show a flowchart of the method for surface-modifying asensor device in Example 1 of the present invention;

FIG. 1E show a perspective view of a sensor device in Example 2 of thepresent invention;

FIG. 2A is a FTIP (Fourier transform infrared spectroscopy) spectrum ofthe sensor device of Comparative Example 1 in Test Example of thepresent invention; and

FIG. 2B is a FTIP spectrum of the sensor device of Example 1 in TestExample of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Because of the specific embodiments illustrating the practice of thepresent invention, one skilled in the art can easily understand otheradvantages and efficiency of the present invention through the contentdisclosed therein. The present invention can also be practiced orapplied by other variant embodiments. Many other possible modificationsand variations of any detail in the present specification based ondifferent outlooks and applications can be made without departing fromthe spirit of the invention.

The drawings of the embodiments in the present invention are allsimplified charts or views, and only reveal elements relative to thepresent invention. The elements revealed in the drawings are notnecessarily aspects of the practice, and quantity and shape thereof areoptionally designed. Further, the design aspect of the elements can bemore complex.

Example 1

With reference to FIG. 1A to 1D, there is a flowchart of a method forsurface modifying a sensor device in the present invention.

First, as shown in FIG. 1A, a sensor device 20 is provided and it has ametal film 21 disposed on a surface thereof. In the present example, thesensor device 20 is an optical fiber sensor device such as aside-polishing optical fiber sensor device, and its surface has asensing area. On the surface of the sensing area, a gold film is formedby the method of depositing metal films such as sputtering and serves asthe metal film 21.

Subsequently, as shown in FIG. 1B, a surface modification layer 23having a plurality of carboxyl groups is formed on the metal film 21 ofthe sensor device 20 by isopropyl alcohol plasma. In the presentexample, the isopropyl alcohol plasma is carried on in the followingmanner. Isopropyl alcohol is used as material gas and introduced in to avacuum discharge tube. Discharging ionizes isopropyl alcohol and thenvarious chemical active species are produced. After complex chemicalreactions, products are deposited on the metal film 21 of the sensordevice 20 to form a surface modification layer 23 having a plurality ofcarboxyl groups. Therefore, the metal film 21 of the sensor device 20 ismodified to obtain many carboxyl groups thereon. The surfacemodification layer 23 formed thereby has low thickness and porosity, andevenly covers the surface of the metal film 21 of the sensor device 20.

Then, as shown in FIGS. 1C and 1D, acrylic acid is used as a monomer andgrafting polymerization thereof is performed under UV illumination.Hence, acrylic acid monomers are grafted to the carboxyl groups of thesurface modification layer 23 and forms a poly(acrylic acid) layer 24.

Example 2

First, as mentioned in Example 1, the surface of the sensor device 20 ismodified to form the surface modification 23 and the poly(acrylic acid)layer 24 on the metal film 21 of the sensor device 20.

Subsequently, as shown in FIG. 1E, the carboxyl groups of thepoly(acrylic acid) layer 24 is activated by a coupling activator. Pluralbiomolecules 24 are provided and their amino groups are bonded to thecarboxyl groups of the poly(acrylic acid) layer 24 to form a biomoleculelayer. In the present invention,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is used as the couplingactivator.

Comparative Example 1

In the manner similar to that mentioned in Example 1, the metal film 21of the sensor device 20 is surface-modified. However, surfacemodification employs only isopropyl alcohol plasma.

Test Example

Fourier transform infrared spectroscopy analysis (FTIP analysis) is,performed to test the sensor devices made in Example 1 and ComparativeExample 1, and their results are respectively shown in FIGS. 2A and 2B.FIG. 2A shows the FTIP spectrum of the sensor device of ComparativeExample 1 (only surface-modified by isopropyl alcohol plasma). FIG. 2Bshows the FTIP spectrum of the sensor device of Example 1(surface-modified by isopropyl alcohol plasma and graftingpolymerization of acrylic acid).

According to the FTIP spectrums, the sensor device of Example 1(surface-modified by isopropyl alcohol plasma and graftingpolymerization of acrylic acid) has more carboxyl groups and hydrophilicfunctional groups such as hydroxyl groups than that of ComparativeExample 1 (only surface-modified by isopropyl alcohol plasma).

In conclusion, if a metal film is formed evenly by sputtering on thesurface of the sensor device, SPR response can occur thereon. When asurface modification layer having carboxyl groups is formed on the metalfilm by isopropyl alcohol plasma, and acrylic acid used as a monomer isgrafted to the carboxyl groups under UV illumination and thenpolymerized to form a poly(acrylic acid) layer, the functional groups ofthe metal film of the sensor device can be modified by theabovementioned mixture of the chemical films of the present invention.The increase on the number of the carboxyl groups on the surface canenhance the subsequent immobilization of the biomolecules and alsohydrophilicity of the surface of the sensor device. Furthermore, sincethe immobilization of the biomolecules is enhanced, the detectionefficiency can be improved and detection accuracy and reaction speed canboth advanced.

Although the present invention has been explained in relation to itspreferred embodiment, it is to be understood that many other possiblemodifications and variations can be made without departing from thescope of the invention as hereinafter claimed.

1. A method for surface-modifying a sensor device comprising thefollowing steps: providing a sensor device, wherein a surface of thesensor device has a metal film; forming a surface-modification layerhaving a plurality of carboxyl groups on the metal film of the sensordevice by isopropyl alcohol plasma; and forming a poly(acrylic acid)layer on the surface-modification layer, wherein the acrylic acid of thepoly(acrylic acid) layer is grafted to the carboxyl groups of thesurface-modification layer.
 2. The method as claimed in claim 1, furthercomprising the following step: forming a bio-molecule layer on thepoly(acrylic acid) layer, wherein bio-molecules of the bin-moleculelayer are bonded to the carboxyl groups of poly(acrylic acid) of thepoly(acrylic acid) layer.
 3. The method as claimed in claim 2, whereinthe biomolecules are protein A or serum albumin.
 4. The method asclaimed in claim 2, wherein the biomolecules of the bio-molecule layerare bonded to the poly(acrylic acid) layer in the presence of a couplingactivator.
 5. The method as claimed in claim 1, wherein the metal layeris a gold or silver layer.
 6. The method as claimed in claim 1, whereinthe poly(acrylic acid) layer grafted to the carboxyl groups of thesurface-modification layer is formed by the polymerization of acrylicacid under UV illumination.
 7. A surface-modified sensor device,comprising: a sensor device, on which a metal film is disposed; asurface-modification layer having a plurality of carboxyl groups on themetal film of the sensor device, wherein the surface-modification layeris formed by isopropyl alcohol plasma; and a poly(acrylic acid) layer onthe surface-modification layer, wherein the acrylic acid of thepoly(acrylic acid) layer is grafted to the carboxyl groups of thesurface-modification layer.
 8. The surface-modified sensor device asclaimed in claim 7, further comprising: a bio-molecule layer located onthe poly(acrylic acid) layer, wherein bio-molecules of the bio-moleculelayer are bonded to the carboxyl groups of poly(acrylic acid) of thepoly(acrylic acid) layer.
 9. The surface-modified sensor device asclaimed in claim 8, wherein the biomolecules are protein A or serumalbumin.
 10. The surface-modified sensor device as claimed in claim 8,wherein the biomolecules of the bio-molecule layer is bonded to thepoly(acrylic acid) layer in the presence of a coupling activator. 11.The surface-modified sensor device as claimed in claim 7, wherein themetal layer is a gold or silver layer.
 12. The surface-modified sensordevice as claimed in claim 7, wherein the poly(acrylic acid) layergrafted to the carboxyl groups of the surface-modification layer isformed by the polymerization of acrylic acid under UV illumination.